The goal of our program is to understand the function of two-component histidine kinases in the fungi Neurospora crassa and Candida albicans. Nik-1 and Cos1p are homologs and both are important during hyphal development in their respective organisms. We plan to define the other signaling proteins in each of the signal transduction pathways, analyze the biochemical properties of each protein, and determine the cell wall composition of wild type and knockout mutant organisms. As C. albicans is a pathogen, these studies should help define possible antifungal targets, as hyphal development is correlated with virulence in this organism. We will use N. crassa as a model for Cos1p function in C. albicans due to the ease of genetic manipulation in this organism. Nik-2 is another histidine kinase in N. crassa whose function is unknown and is not found in C. albicans. We will construct a null mutant and analyze the resultant phenotype. In addition we plan to define the other proteins in the Nik-2 signal transduction pathway and isolate the protein and analyze its biochemical proteins For all of the above proteins, we will also attempt to grow crystals with the hope of obtaining a three-dimensional structure.